title: Model-based approach to describe G-CSF effects in carboplatin-treated cancer patients.
abstract: OBJECTIVE
  Granulocyte colony-stimulating factor (G-CSF) is often used in cancer patients receiving cytotoxic drugs to prevent or reduce high grade neutropenia. We propose a pharmacokinetic/pharmacodynamic model to describe myelotoxicity in both G-CSF treated and non-treated patients that shall increase our understanding of G-CSF effects.
  
  
  METHODS
  The model was built from absolute neutrophil counts (ANC) obtained in 375 carboplatin-treated patients, 47 of whom received G-CSF. It includes some prior information on G-CSF taken from the literature. Simulations were performed to understand differences in G-CSF effects and explore the impact of G-CSF formulation.
  
  
  RESULTS
  Our model well described the data in all patients. Model simulations showed that G-CSF was not as beneficial as expected in some patients. Furthermore, a longer and stronger effect was observed for the pegylated formulation in comparison with the daily standard formulation even if the latter was given for 11 consecutive days.
  
  
  CONCLUSIONS
  The proposed model allows a mechanistic interpretation of G-CSF effects on ANC and raises the question of a systematic beneficial effect of G-CSF treatment. Other studies are needed to confirm these findings and help identifying patients for whom G-CSF is beneficial.
authors.affiliation: Unité de Médecine, Urgences Soins Intensifs, Université de Toulouse, INP, Ecole Nationale Vétérinaire de Toulouse, 31076, Toulouse, France, m.pastor@envt.fr.
authors.forename: Mélanie L
authors.initials: ML
authors.lastname: Pastor
authors.forename: Céline M
authors.initials: CM
authors.lastname: Laffont
authors.forename: Laurence
authors.initials: L
authors.lastname: Gladieff
authors.forename: Antonin
authors.initials: A
authors.lastname: Schmitt
authors.forename: Etienne
authors.initials: E
authors.lastname: Chatelut
authors.forename: Didier
authors.initials: D
authors.lastname: Concordet
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D016190:Carboplatin / Q000627:therapeutic use*; D003198:Computer Simulation; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D009504:Neutrophils / Q000187:drug effects / Q000473:pathology; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D016179:Granulocyte Colony-Stimulating Factor; D016190:Carboplatin